Uranium is a natural, radioactive heavy metal, widely used in the nuclear industry in various chemical and isotopic forms. Its use in the fuel cycle involves the risk of radiological exposure for the workers, mainly via the inhalation of uranium particles. According to the workplace configuration, uranium contaminations can be acute or repeated, involve various chemical forrns and different levels of enrichment, as well as involving one or several components. The dosimetric concepts and models available for workers' radiological protection, as well as most of the studies of the biological effects, correspond to acute exposure situations. Moreover the processes leading to pathological effects are little known in vivo. In this context, the main question is to know whether exposures due to repeated inhalation by rats induce the element's kinetics and toxicity, which may be different from those observed after an acute exposure.

In this study, comparison of the experimental and theoretical biokinetics of an insoluble uranium repeatedly inhaled over three weeks shows that a chronic contamination is correctly modelled, except for bone retention, by the sum of acute, successive and independent incorporations. Moreover the kinetics of a soluble uranium inhaled irregularly can be modified by previous repeated exposure to an insoluble uranium. In certain cases therefore, exposure to uranium could modify i t s biokinetics during later exposures.

At a toxicological level, the study demonstrates that the uranium particles inhaled repeatedly induce behavioural disruptions and genotoxic effects resulting in various sorts of DNA damage, in several cell types and certainly depending on the quantity inhaled. Exposures involving several uraniferous components produce a synergy effect. Moreover, repeated inhalations worsen the genotoxic effects in comparison to an acute exposure.

This work demonstrates the importance of not ignoring the effects of the repetition of uranium exposure. It will provide the bases for an improvement of the radiological protection system allowing optimization of the monitoring of nuclear industry workers. In the wider context, this work helps to enlarge our knowledge of particle toxicity.